This invention relates to apparatus and methods useful for biochemical analysis. More specifically, this invention relates to a highly automated capillary electrophoresis apparatus for the simultaneous analysis of multiple samples, and methods for using such apparatus.
Capillary electrophoresis (CE) is a powerful analytical separation technique that brings speed, quantitation, reproducibility and automation to the inherently highly resolving but typically labor intensive methods of electrophoresis (e.g., Capillary Electrophoresis Theory and Practice, Grossman and Colburn, eds., Academic Press (1992)). While early capillary electrophoresis systems utilized only a single capillary tube, multi-capillary systems have been developed to provide increased throughput (e.g., Mathies et al., U.S. Pat. No. 5,247,240; Dovichi and Zhang, U.S. Pat. No. 5,439,578; Kambara, U.S. Pat. No. 5,516,406; Takahashi, et al., Anal. Chem., 66: 1021-1026 (1994)). Such multi-capillary CE systems are particularly attractive for use in large scale DNA sequencing projects.
However, existing multi-channel capillary electrophoresis systems have several significant shortcomings that limit their utility, particularly for applications requiring a high degree of automation, throughput, detection sensitivity and reliability. For example, existing systems do not provide for a sheath-flow detection cuvette wherein a capillary array may be replaced by a user without extensive disassembly of the cuvette. In addition, existing systems do not provide for a sheath-flow detection cuvette wherein fresh separation media and/or capillary wash solutions may be introduced into outlets of the capillary tubes under high pressure. Thus, there remains a continuing need for an automated multi-channel capillary electrophoresis device including these features.
The present invention is directed towards our discovery of a multi-channel capillary electrophoresis device including a sheath-flow detection cuvette wherein a capillary array is easily replaceable by a user, and wherein fresh separation media and/or capillary wash solutions may be introduced into outlets of the capillary tubes under high pressure.
In a first aspect, the invention comprises a multi-channel capillary electrophoresis apparatus. The apparatus includes a capillary array assembly comprising a plurality of capillaries, each capillary having an outlet, and an outlet support for supporting the capillary outlets. In addition, the apparatus includes a cuvette defining a receiving slot, a gap region, and a detection zone, where the receiving slot of the cuvette is adapted to removably receive the outlet support. When the outlet support is inserted into the receiving slot, the capillary outlets are positioned in the gap region in proximity to the detection zone, and a flow channel is formed by the outlet support and the receiving slot such that the flow channel is in fluid communication with the gap region. The apparatus further includes a plumbing block in fluid communication with the flow channel for supplying a fluid flow through the gap region sufficient to transport material downstream from the capillary outlets to the detection zone.
These and other features and advantages of the present invention will become better understood with reference to the following description, drawings, and appended claims.